JC virus (JCV) is an oncogenic human papovavirus that has been postulated to be involved in the formation of glial tumors in patients with progressive multifocal leukoencephalopathy (PML). The incidence of PML is increased significantly in AIDS patients. It was of interest, therefore, to investigate the interaction of HIV and JCV. We initiated these studies by analyzing the effect of the HIV tat gene product on JCV viral gene expression. Using a combination of cotransfection assays and in vitro DNA binding assays, we have demonstrated that tat activates early gene expression at the transcriptional level. At least part of the increase in transcription is a result of activation of transcription factors which interact with the tissue-specific JCV enhancer. Investigations are underway to determine if the activation is due to the increased synthesis or change in specific activity of existing transcription factors.